Efficacy of a phage cocktail in controlling phage resistance development in multidrug resistant Acinetobacter
Yuyu Yuan1, Lili Wang2, Xiaoyu Li2
1School of Bioengineering, Dalian University of Technology, Dalian, 116024, China.
Abstract:
The control and treatment of multidrug resistant pathogens infections has become a grand challenge for clinicians worldwide. Virulent phage has long been considered as an effective bactericidal agent, which may be a potentially alternative to antibiotics. However, the rapid development of phage resistance seriously hinders the wide and continuous application of virulent phages. In this study, Acinetobacter baumannii phage vB_AbaS_D0 was isolated, characterized and used to control the phage resistance development in bacterial strains. Transmission electron microscopy analysis of vB_AbaS_D0 indicated it belonged to the Siphoviridae family with an icosahedral head. Its whole genome was 43, 051 bp in size, with a GC content of 45.48% and 55 putative open reading frames. The data showed that vB_AbaS_D0 was a virulent phage. Although vB_AbaS_D0 had a very weak bactericidal activity, a wide range of Acinetobacter baumannii strains were sensitive to it. The results suggested that the cocktail of vB_AbaS_D0 and another Acinetobacter baumannii phage vB_AbaP_D2 could improve the therapeutic efficacy in vivo and in vitro. The resistance mutation frequency of A. baumannii cells infected with D0 or phage cocktail was significantly lower than cells treated with D2 (P < 0.01). Phage therapy in the murine bacteremia model results showed that the percentage of phage resistant mutant occurrence in the phage D0 or cocktail treatment group was significantly lower than in phage D2 treatment group (P < 0.01).
Insights
Phage therapy using Acinetobacter baumannii phage D0, alone or in a cocktail, significantly reduces bacterial resistance compared to phage D2. This offers a promising strategy against multidrug-resistant infections.
Area of Science:
- Microbiology
- Virology
- Infectious Diseases
Background:
- Multidrug-resistant pathogens pose a significant clinical challenge globally.
- Bacteriophages (phages) are potential alternatives to antibiotics for treating bacterial infections.
- Phage resistance development limits the efficacy of phage therapy.
Purpose of the Study:
- To isolate and characterize Acinetobacter baumannii phage vB_AbaS_D0.
- To evaluate the efficacy of phage D0 and a phage cocktail in controlling phage resistance.
- To assess the therapeutic potential against Acinetobacter baumannii infections.
Main Methods:
- Isolation and characterization of Acinetobacter baumannii phage vB_AbaS_D0.
- Transmission electron microscopy and whole-genome sequencing of the phage.
- In vitro and in vivo experiments using phage D0, phage D2, and a phage cocktail.
- Murine bacteremia model to assess therapeutic efficacy and resistance development.
Main Results:
- Phage vB_AbaS_D0, a virulent phage of the Siphoviridae family, was characterized.
- A cocktail of phages D0 and D2 demonstrated improved therapeutic efficacy.
- Significantly lower phage resistance mutation frequency was observed with phage D0 or the cocktail compared to phage D2.
Conclusions:
- Phage D0 and its combination therapy show potential in overcoming phage resistance in Acinetobacter baumannii infections.
- Phage cocktails can enhance therapeutic outcomes and mitigate resistance development.
- This study provides a basis for developing effective phage-based strategies against multidrug-resistant bacteria.
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